Several ′rasayana′ herbs that are enlisted in Indian system of medicine have been in use for the treatment of age-related neurodegenerative disorders including Alzheimer′s disease (AD). Roots of Argyreia speciosa are used in several Ayurvedic preparations as brain tonic and nervine tonic. The present work was undertaken to justify the traditional claim of the plant as nootropic and antiamnesic agent in mice. The ethyl acetate and ethanolic fractions (EtAS) of roots were selected for the study. Exteroceptive behavioural models such as elevated plus maze and Water maze were used to assess the short-term memory, whereas, scopolamine and natural ageing- induced amnesia served as interoceptive models. The whole brain acetyl cholinesterase activity was measured to assess the effect of A. speciosa on the central cholinergic system. Scopolamine (0.4 mg/kg, i.p.) increased the transfer latency significantly ( P< 0.01) in young mice on the first and second day as compared to control indicating the impairment of memory. Pretreatment with EAAS (100 and 200 mg/kg, p.o.) significantly ( P< 0.01) attenuated scopolamine and ageing-induced amnesia. Escape latency time was recorded in the water maze model as an index of acquisition, and trials were conducted for 4 days. The mean time spent in target quadrant (TSTQ) during retrieval trial on fifth day was taken as the index of retrieval (memory). EAAS (100 and 200 mg/kg, p.o.) administered before the training trial (from day 1 to day 4), significantly ( P< 0.01) attenuated scopolamine and ageing-induced decrease in TSTQ during the retrieval test on the fifth day. EAAS (100 and 200 mg/kg, p.o.) significantly produced reduction in whole brain acetyl cholinesterase (AChE) activity of both young and aged mice thus exhibiting anti-AChE activity in whole brain homogenate compared to Piracetam, scopolamine and control groups of mice. The results indicate that A. speciosa has significant nootropic and antiamnesic activity, justifying its traditional use in Ayurveda.